OBJECTIVE. To investigate the association between population structure and the pandemic influenza A (H1N1) 2009 epidemic in a spatial context. DESIGN. A retrospective case-report series study. SETTING. Hong Kong. PATIENTS. Laboratory-confirmed cases of human influenza A (H1N1) 2009 reported to the Centre for Health Protection between May and September 2009. MAIN OUTCOME MEASURES. A geo-referenced database was established comprising age, gender, and residence location of all influenza A (H1N1) 2009 cases reported in the first 5 months of the Kong Kong epidemic's first wave in 2009. They were divided into four age categories: infant, student, adult, and elderly. Correlation coefficients and odds ratios were calculated to explore the association of H1N1 cases with population configurations in 400 District Council Constituency Areas. RESULTS. Of the 24 414 H1N1 cases reported, students accounted for the highest proportion (54.6%), followed by adults (33.4%), infants (11.1%), and the elderly (0.9%). Transmission was initially concentrated in students which then extended to infants and adults. Except for the elderly, the total population size and that of each age category were significantly associated with the H1N1 cases spatially. Mobility indicators as reflected by the number of students studying outside and adults working outside residential District Council Constituency Areas were also positively associated with H1N1 cases. CONCLUSIONS. Local population structure and mobility were associated with the spatial distribution of the H1N1 epidemic, despite the small size of the territory of Hong Kong. If an influenza epidemic hits again, an examination of these factors spatially would be useful in supporting the planning of interventions.